Jin Haidan, Ji Meiying, Chen Liyan, Liu Qixiang, Che Shuanlong, Xu Ming, Lin Zhenhua
Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China.
Department of Biochemistry, Yanbian University Medical College, Yanji, 133002, China.
J Exp Clin Cancer Res. 2016 Mar 9;35:42. doi: 10.1186/s13046-016-0316-0.
Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. This study aims to investigate the Mortalin expression in breast cancer and its correlation with the outcome of the patients with breast cancer.
A total of 155 invasive ductal carcinoma of breast patients with strict follow-up, 52 ductal carcinoma in situ (DCIS) and 45 adjacent non-tumor breast tissues were selected for immunohistochemical (IHC) staining of Mortalin protein. The localization of Mortalin protein was detected in MDA-MB231 breast cancer cells using immunofluorescence (IF) staining. The correlations between overexpression of Mortalin and the clinical features of patients with breast cancer were evaluated using chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models.
Mortalin protein showed a mainly cytoplasmic staining pattern in breast cancers by using IHC staining in paraffin embedded breast cancer tissues and IF staining in MDA-MB231 breast cancer cells. The strongly positive rate of Mortalin protein was 63.9% (99/155) in invasive ductal carcinoma of breast and was significantly higher than in DCIS 34.6% (18/52) and adjacent non-tumor tissues 15.6% (7/45). Overexpression of Mortalin was closely correlated with histological grade, clinical stage, lymph node metastasis, lower disease free survival (DFS) and overall survival (OS) rates of patients with breast cancer. Moreover, multivariate analysis suggested that Mortalin emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.
Mortalin is upregulated in breast cancer, and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.
Mortalin/GRP75是一种普遍存在的线粒体伴侣蛋白，与胞质热休克蛋白70（HSP70）相关，并在肿瘤发生中起作用。本研究旨在探讨Mortalin在乳腺癌中的表达及其与乳腺癌患者预后的相关性。
选取155例有严格随访的浸润性导管癌患者、52例导管原位癌（DCIS）患者和45例相邻的非肿瘤乳腺组织进行Mortalin蛋白的免疫组织化学（IHC）染色。采用免疫荧光（IF）染色检测Mortalin蛋白在MDA-MB231乳腺癌细胞中的定位。采用卡方检验和Fisher精确检验评估Mortalin过表达与乳腺癌患者临床特征之间的相关性。采用Kaplan-Meier法计算生存率，并通过Cox比例风险模型分析预后因素与患者生存之间的关系。
通过对石蜡包埋的乳腺癌组织进行IHC染色以及对MDA-MB231乳腺癌细胞进行IF染色，发现Mortalin蛋白在乳腺癌中主要呈细胞质染色模式。Mortalin蛋白在浸润性导管癌中的强阳性率为63.9%（99/155），显著高于DCIS中的34.6%（18/52）和相邻非肿瘤组织中的15.6%（7/45）。Mortalin的过表达与乳腺癌患者的组织学分级、临床分期、淋巴结转移、较低的无病生存率（DFS）和总生存率（OS）密切相关。此外，多因素分析表明，Mortalin与临床分期和Her2表达状态一起，成为乳腺癌患者重要的独立预后因素。
Mortalin在乳腺癌中上调，可能是一个有用的预后不良生物标志物，也是乳腺癌患者潜在的治疗靶点。
